Efficient typing of copy number variations in a segmental duplication-mediated rearrangement hotspot using multiplex competitive amplification
Efficient typing of copy number variations in a segmental duplication-mediated rearrangement hotspot using multiplex competitive amplification
复制标题
使用多重竞争扩增对片段复制介导的重排热点中的拷贝数变异进行有效分型
DOI：
10.1038/jhg.2012.66
复制
发表时间：
2012-08-01
影响因子：
3.5
通讯作者：
Zhang, Feng
中科院分区：
文献类型：
--
作者：
Du, Renqian;Lu, Chuncheng;Zhang, Feng
局部基因组结构，如片段重复（SD），可以诱导拷贝数变异（CNV）在人类基因组中的热点，其中许多表现为基因组疾病。全基因组CNV研究已经取得了重大的技术进步，但这些昂贵的方法不适合对某些疾病相关的CNV或人群中其他感兴趣的基因座进行基因分型。最近，两项独立的研究表明，小鼠减数分裂表达基因1（Meig 1）对精子发生至关重要。我们发现，人类直系同源物MEIG 1的侧翼是一个SD对，在SD对之间的非等位基因同源重组（NAHR）可以导致复发性CNV。为了研究这种潜在的CNV热点及其在精子发生中的作用，我们开发了一种新的CNV基因分型方法，AccuCopy，基于多重竞争扩增，调查320例生精障碍患者和93名健康对照。三个MEIG1重复（两个在患者和一个在对照组）被确定，而没有deletionwasfound.As NAHR的结果在更多的复发性缺失比重复在一个位点上，重复MEIG1重复的过度代表性表明一个潜在的纯化选择在这个热点上操作，可能通过繁殖力。我们还表明AccuCopy是一种有效和可靠的多重CNV基因分型方法。
Local genomic architecture, such as segmental duplications (SDs), can induce copy number variations (CNVs) hotspots in the human genome, many of which manifest as genomic disorders. Significant technological advances have been achieved for genome-wide CNV investigations, but these costly methods are not suitable for genotyping certain disease-associated CNVs or other loci of interest in populations. Recently, two independent studies showed that the murine meiosis expressed gene 1 (Meig1) was critical to spermatogenesis. We found that the human orthologue MEIG1 is flanked by an SD pair, between which non-allelic homologous recombination (NAHR) can cause recurrent CNVs. To study this potential CNV hotspot and its role in spermatogenesis, we developed a new CNV genotyping method, AccuCopy, based on multiplex competitive amplification to investigate 320 patients with spermatogenic impairment and 93 healthy controls. Three MEIG1 duplications (two in patients and one in controls) were identified, whereas no deletion was found. As NAHR results in more recurrent deletions than duplications at a locus, the over representation of recurrent MEIG1 duplications suggests a potential purifying selection operating on this hotspot, possibly via fecundity. We also showed that AccuCopy is an efficient and reliable method for multiplex CNV genotyping.